Had Govt. of India taken action in Maiden Pharma Kundli (Sonipat) case -Zambia tragedy-

Gustakhi Maaf Haryana- Pawan Kumar Bansal.

Had Govt. of India taken action in Maiden Pharma Kundli (Sonipat) case -Zambia tragedy- Deaths in MP and Rajsthan perhaps could have averted. To show our image as Pharma King abroad and monetary benefits, the issue was buried under carpet.

Whenever DEG poisoning in cough syrup occurs, we do all investigations regarding the episode, casualties and other related issues but every time main issue buried is under carpet trying to keep our PHARMA KING IMAGE-INTACT. . Again and again our GMP or WHO-GMP drug mfg. firms are caught manufacturing medicines that too for children with deadly/toxic excipients (solvents) not to heal them but to kill them. Everyone in the pharma trade who manufacture liquid oral syrup knows about PG&DEG (PROPYLENE GLYCOL & DIETHYLENE GLYCOL).

G.L.Singal retired Haryana State Drug Controller told “that more than 15 cases of DEG Poisoning reported in the last century over the Globe, since 1937, (including 4-5 cases in India in last around 40 years – leading to more than 100 children lost their lives) and deaths due to DEG contamination have been reported at JJ Hospital Bombay, Chennai, Odisha, Bihar, Gurgaon (1998), Udhampur (2020), Sonepat & now at Madhya Pardesh and Rajasthan.have occurred but no lesson taken adding that since paracetamol and some drugs like dextromethorphan used commonly in liquid oral cough preparations does not dissolve in water; , drug makers use solvent like Propylene Glycol (PG) to dissolve such water insoluble drugs to make the cough syrup?” This solvent has DEG/EG as impurities, which is mandatorily required to be tested for its absence before use as solvent in the mfg. of cough syrup.

DEG-which is an automobile/Plastic industry solvent and a cheap /good substitute for Propylene Glycol is also routinely mixed with Propylene Glycol (to reduce the cost) or sometimes is used in place of PG as solvent. DEG is toxic and fatal chemical responsible for the casualties reported so far in cough syrup cases. As per the report shared by Tamil Nadu Govt. with Madhya Pardesh Govt. after this tragedy in MP, the alleged cough syrup found containing 48.6% DEG- such high percentage of DEG indicates that the drug was appeared to have been dissolved in DEG by the drug maker and PG was not at all used.

Every drug firm is mandated to test PG for diethylene glycol and other impurities before using it for cough syrups but for many reasons (cost of testing, unavailability of equipment’s, reference materials, technical knowhow etc.) this test is not done and untested PG is used either in “good faith” of raw material supplier or inadvertently or intentionally with casual approach and proves fatal. Most disturbing part is that in such cases, we do have the reasons for happening of such large no of causalities and also we have all the means to prevent their re-occurrences but still such casualties do re-occur. This is third such tragedy in last around 5 years in INDIA only-THE PHARMACY OF WORLD- We are yet to learn a lesson and find ways –Though it is not a unknown virus or microbes or unknown disease which need extensive studies, human trials etc. to tackled with. We have the remedy with us which is open and known to everyone but still our poor children are made scapegoats. We rather than protecting lives of innocent children are engaged in protecting our image of GLOBAL PHARMACY.

FOLLOWING MAJOR REASONS CAN BE CITED FOR SUCH TRAGDIES & RE-OCCURENCES

* Cost cutting: – we are master in cost management even when we are dealing in human lives (we do not bother).
* It is well known in pharmaceutical trade that formulation or dosage form are available at a cost lower than cost of raw material which otherwise is out of imagination.
* We as formulator (Manufacturer) do not bother about role, importance, safety etc. of excipients (inactive raw materials) resulting in such tragedies.
* Drugs which are water insoluble like paracetamol, dextromethorphan etc. need some solvent (other than water) to solubilize it. Otherwise the final product will not be a syrup product (which is commonly preferred as compared to suspension) Therefore need for such solvents like PG
* PG is good solvent commonly used in oral liquids/ parenteral, but costlier than water and cost of final product shoot up consequently. (PG up to 30- 50 % is normally used in making liquid oral syrups)
* DEG/EG is commercial available in the market which is a viscous, colourless, sweet tasting liquid -anti-freeze and used in various polyester/pet industry) available at less than half of rate of PG- also solubilise these water insoluble drugs.
* DEG/EG sometime used inadvertently or without knowing its consequences or as an admixture but with sole motto of cost reduction. Sometimes PG supplier (who is RM trader) supplies PG to pharm. manufacturing firm as adulterated with DEG. However, syrups containing low percentage of DEG (traces) are not fatal.

MISCELLENEOUS REASONS

1. LACK OF INFRASTRUCTURE:-

Drug manufacturing is now a day’s not a small scale concept. Manufacturing of quality drugs as the federal requirement is practically impossible with SSI or MSME. There are practical instances when we do not have laboratory test equipment, reagents, chemicals, reference materials, technical knowhow etc. may be for being costly(beyond reach) or otherwise unavailable but we continue manufacturing for so many reasons simultaneously without anticipating for the consequences- might be lives of many at stake. Sometimes we do not have required technical knowhow and manufacture drugs by hit and trial putting again lives on stake.

We lack adequate technical knowledge leading to casualties. Some of drug manufacturing firms do not test excipients, solvents etc. and some only perform the tests which can be tested easily in their own lab, having meagre importance to raw material testing. But in pharmaceutical industry every material (Raw material, Packing Material, Solvent, Water etc.) is of immense importance and their quality is paramount while manufacturing medicines.

2. DRUG REGULATORY ISSUES

Although we have the Central and State regulatory network but it is hard to believe that these agencies are having set up machineries and other things to justify their role in safeguarding human lives. No, as per the recent and past incidences of cough syrup. There are many instances where we come to know that mfg. units are ordered to be closed for noncompliance of regulatory norms but no unit found ordered to be closed for using DEG or not testing DEG in PG or not having reference impurity or not having GC. Some unit gets this test of Propylene Glycol outsourced from some private approved test Laboratories whose reports are not at all trustworthy but such reports are good for legal compliance

3. CASUAL APPROACH:-

Medicine once released for sale in the market can create havoc because one unit dosage form can take one life, therefore any laxity or casual approach in manufacturing operation is not at all desirable/acceptable. Some manufacturer do take very casual approach while manufacturing medicines without anticipating for the outcome of their casual approach. Purchasing raw and packing materials from unauthorised source, use without mandatory testing, non -compliances to various GMP norms and manipulations in the record keeping

WHAT CAN BE REMEDIES:-

* SLA should discourage granting permissions drug manufacturers to manufacture cough syrups containing those with PG –as solvent. They should encourage manufacturer to manufacture cough syrup without using PG as solvent (they can use alternate solvents or co-solvents) and should try to develop solvents other than PG to make drugs that cannot dissolve in water.

* Right now drug makers are required to test only raw materials as per standards prescribed in pharmacopoeias/others standards. Guidelines can be issued saying whosoever makes drug formulations using PG must release the batch after testing the final finished product for DEG and other impurities.

* While granting approval to manufacture PG based liquid cough syrups, the SLA should ensure that the manufacturing firm has the testing facilities, technical knowhow and reference material for testing including of these impurities, otherwise approval be rejected. Although this is provided under the D&C Rules but not adhered to by many SLAs

* Guidelines can be issued to the drug manufacturer that whosoever makes drug formulations using PG must also test the final finished product for DEG and other impurities. So you mandate gas chromatography at both entry and exit levels.